Investigating SX-682 in Combination With Apalutamide in Metastatic Castration-resistant Prostate Cancer

NCT07002320 | Recruiting Phase 1

• 2 other identifiers: CCR60411008729
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 4

Brief Summary

ASpiRE will investigate the effect of the drug SX-682 in combination with Apalutamide in men suffering from metastatic castration-resistant prostate cancer (mCRPC).

Conditions

Metastatic Castrate-Resistant Prostate Cancer (mCRPC)

Keywords

Prostate cancer

Outcome Measures

Primary Outcomes (2)

• Biologically active and tolerable dose range

  The biological active and tolerable combination doses are those that satisfy observed DLT rate\<33% and demonstrate reduction in myeloid derived suppressor cells (MDSCs).

  From start of treatment to end of Cycle 2 Day 1 (each cycle is 28 days)

• Anti-tumour activity of SX-682 when administered with Apalutamide

  Response rate on the basis of Prostate Cancer Working Group 3 (PCWG3), and/or Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

  24 months

Secondary Outcomes (11)

• Safety and tolerability profile as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  12 months

• Steady state pharmacokinetic parameters (CSSmin and CSSMax)

  At the end of Cycle 2 Day 1 (each cycle is 28 days).

• Number of patients with Prostate Specific Antigen (PSA) decline greater than 50%

  24 months

• Soft tissue objective response (CR or PR) by RECIST v1.1

  From date of enrolment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.

• Changes in circulating tumour DNA (ctDNA) tumour fractions (TF).

  24 months

Study Arms (2)

Phase I: Dose Escalation

EXPERIMENTAL

Phase I will identify a biologically active and tolerable (safe) dose range of SX-682 in combination with Apalutamide in patients with metastatic castrate-resistant prostate cancer (mCRPC).

Drug: SX-682; Drug: Apalutamide

Phase II: Dose Expansion

EXPERIMENTAL

Phase I will investigate the anti-tumour activity of tolerable doses of SX-682 in combination with Apalutamide in patients with metastatic castrate-resistant prostate cancer (mCRPC). Patients will be treated at dose levels deemed to be tolerable and biologically active, based on safety and efficacy data from Dose Escalation.

Drug: SX-682; Drug: Apalutamide

Interventions

Apalutamide DRUG

Apalutamide is supplied as 60mg film coated tablets.

Phase I: Dose Escalation; Phase II: Dose Expansion

SX-682 DRUG

SX-682 is supplied as 100mg film coated tablets.

Phase I: Dose Escalation; Phase II: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and be capable of cooperating with treatment.
• Age ≥ 18 years.
• Histologically or biochemically confirmed adenocarcinoma of the prostate and with tumour tissue accessible for research analysis for this trial. Patients who have no histological diagnosis must be willing to undergo a biopsy to prove prostate adenocarcinoma.
• Patients recruited to phase 1 dose escalation cohorts must have biopsiable disease and consent to mandatory pre- and post-treatment biopsies (baseline and on Cycle 2 Day 1).
• Metastatic castration-resistant prostate cancer.
• All patients must have documented resistance to 1 prior next generation antiandrogen therapy (NAAT) defined as:
• For phase 1 and phase 2 Cohorts:
• Patients who have progressed after either enzalutamide, Apalutamide or darolutamide (having received a minimum of 12-weeks of enzalutamide, Apalutamide or darolutamide) will enter phase 1 or phase 2 cohorts directly. Patients that have previously received abiraterone but not an AR antagonist should receive a lead-in with Apalutamide on trial and receive the combination on progression through the lead-in.
• Documented prostate cancer progression as assessed by the investigator with RECIST v1.1 and PCWG3 criteria (Section 3.5) with at least two of the following criteria:
• Progression of soft tissue/visceral disease by RECIST v1.1 and/or,
• Progression of bone disease by PCWG3 bone scan criteria and/or,
• Progression of PSA by PCWG3 PSA criteria.
• PSA ≥ 10ng/ml.
• Received prior castration by orchiectomy and/or ongoing luteinizing hormone releasing hormone agonist treatment.
• Ongoing androgen deprivation with serum testosterone \< 50 ng/dL (\< 1.7 nM).

You may not qualify if:

• Surgery, chemotherapy, or other anti-cancer therapy within 4 weeks prior to trial entry/randomisation into the study (with the exception of abiraterone, enzalutamide, Apalutamide or darolutamide). Any other therapy for prostate cancer, other than gonadotropin releasing hormone analogue therapy, such as progesterone, medroxyprogesterone, progestins or 5-alpha reductase inhibitors, must be discontinued at least 2 weeks before the first dose of the study drug.
• Participation in another interventional clinical trial of an IMP within 4 weeks prior to trial entry. Participation in trials of licensed medications is allowed provided the medication is not a prohibited concomitant medication.
• Prior limited field radiotherapy within 2 weeks and wide field radiotherapy within 4 weeks prior to trial entry.
• Clinical and/or biochemical evidence of hyperaldosteronism or hypopituitarism.
• History of seizures or other predisposing factors including, but not limited to, underlying brain injury, stroke, primary brain tumours, brain metastases and leptomeningeal disease, or alcoholism.
• Malabsorption syndrome or other condition that would interfere with enteral absorption.
• Any of the following cardiac criteria:
• QTcF interval \> 470 msec.
• Clinically important abnormalities including rhythm, conduction, or electrocardiogram (ECG) changes (left bundle branch block, third degree heart block).
• Factors predisposing to QT prolongation including heart failure, hypokalaemia, congenital long QT syndrome, family history of prolonged QT syndrome, unexplained sudden death (under 40) and concomitant medications known to prolong QT interval.
• Coronary artery bypass, angioplasty, vascular stent, myocardial infarction, angina, congestive heart failure (NYHA ≥ grade 2) i or transient ischaemic attack) in the last 6 months (see appendix 4 for NYHA scale).
• Uncontrolled hypotension (systolic blood pressure \< 90mmHg).
• Uncontrolled hypertension on optimal medical management.
• Clinically significant history of liver disease (Child-Pugh B or C, viral or other hepatitis, current alcohol abuse or cirrhosis).
• Any other finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect interpretation of the results or renders the patients at high risk from treatment complications, e.g., patients with a hypersensitivity to the active substance or any of the excipients.

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Prostate Cancer UK: collaborator
• Janssen Pharmaceutica N.V., Belgium: collaborator
• Oncology Institute of Southern Switzerland: collaborator
• Syntrix Biosystems, Inc.: collaborator
• Royal Marsden NHS Foundation Trust: collaborator
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• Belfast Health and Social Care Trust: collaborator
• Institute of Oncology Research (IOR): collaborator

Study Sites (4)

Oncology Institute of Southern Switzerland

Bellinzona, CH6500, Switzerland

NOT YET RECRUITING

Belfast Health and Social Care Trust

Belfast, BT9 7AB, United Kingdom

RECRUITING

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust - Drug Development Unit

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Professor Johann de Bono, MB ChB, FRCP, MSc, PhD, FMedSc

  Institute of Cancer Research, United Kingdom

  STUDY DIRECTOR

Central Study Contacts

Aasia Hussain, PhD

CONTACT

02034376301; ASPIRE@icr.ac.uk

Bindumalini Rao Baikady, PhD

CONTACT

02034376033; ASPIRE@icr.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1 will use a 3+3 design to investigate escalating doses of SX-682 in combination with Apalutamide.

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: June 3, 2025
• Study Start: April 28, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

GB (3); CH (1)